tbuckley/cabot-search huggingface dataset:
ACCRU-GI-2008: A phase II randomized study of atezolizumab (Atezo) plus a multi-kinase inhibitor (MKI) versus MKI alone in patients with unresectable advanced hepatocellular carcinoma (aHCC) who previously received atezolizumab plus bevacizumab (Bev).
Authors: Wen Wee Ma, Fang-Shu Ou, Jenny Jing Li, Nguyen H. Tran, Hani M. Babiker, Alexander Revzin, Haidong Dong, Garth D. Nelson, Andrew Ness, Carissa E. Schuster, Jingquan Jia, Tanios S. Bekaii-Saab
Journal: Journal of Clinical Oncology (2022)

TPS4170 Background: IMbrave150 is the first study demonstrating the benefit of anti-PDL1 in the frontline treatment of aHCC, and established Atezo/Bev as a new 1 st line standard for aHCC. There is currently limited evidence to guide subsequent therapy for aHCC patients progressing on Atezo/Bev. ACCRU-GI-2008 is designed to determine the benefit of continuing Atezo into 2 nd line and the safety of Atezo plus a MKI in patients with aHCC who previously received Atezo/Bev. The study is being conducted across 12 centers in the United States (ClincalTrials.gov#: NCT05168163). Methods: This study utilizes a 2:1 randomized phase II design where eligible patients will receive either Atezo/MKI (experimental arm) or MKI alone (control). Patients will be stratified according to the MKI choice (cabozantinib or lenvatinib, per physician’s decision), etiology of HCC (viral vs. non-viral) and alpha-fetoprotein level ( &lt; 400 vs. &gt; = 400 ng/mL). The major eligibility criteria are histological/cytological diagnosis or clinical diagnosis of HCC per the AASLD or WASL 2018 guidelines, has advanced disease not amendable to curative treatment, previously received and progressed on Atezo/Bev, has received only 1 previous line of systemic therapy (2 nd line only), ECOG PS 0-1, Child Pugh Class A, adequate organ reserves and RECIST v1.1 measurable disease; previous MKI for advanced disease is excluded. The primary endpoints are overall survival (OS) and progression free survival (PFS). A total sample size of 122, with 89 PFS events, we will have 80% power to detect an improvement in median PFS from 4 to 7 months, assuming a one-sided significance level of 0.05. With approximately 84 deaths, we will have 80% power to detect an improvement in median OS from 10 to 18 months, assuming a one-sided significance level of 0.05. The overall one-sided significance level, for the study, is 0.1. An OS interim analysis will be conducted at 89 PFS events. Secondary endpoints include objective response, duration of response, and adverse events. Archival tumor and serial blood samples will be collected to evaluate for potential prediction biomarkers and mechanisms of sensitivity/resistance. Baseline and on-treatment tumor biopsy specimens will also be collected from the initial 10 patients of each arm. The study is approved by the ethics committee and enrollment to the study will be underway by Q2/3 2022. Clinical trial information: NCT05168163.
Utilizing an innovative digital collaboration tool to impact shared decision making, health equity and trust with a focus on advance care planning for patients with metastatic breast cancer.
Authors: Kadie Harry, Arabella Sykes, Timothy J. Pluard
Journal: Journal of Clinical Oncology (2022)

e24123 Background: Advance care planning (ACP) has been associated with improved quality of life, increased use of hospice and palliative care, and less use of extreme treatments close to death. These conversations often do not occur and documentation rates of ACP in oncology patients have been as low as 10%, with rates of documentation increasing between 30-40% in intervention studies. The present study aimed to examine the effectiveness of an online Advance Care Appointment Companion (ACAC) collaboration tool to improve communication and elevate trust between MBC patients and their oncologist and increase completion rates of ACP documents. Methods: Data were collected from 48 patients with mean age of 66.9 years (SD = 6.97) with MBC during their medical oncology appointments (Time 1) and three months later (Time 2) at the Koontz Center for Advanced Breast Cancer. At Time 1, patients were enrolled on the ACAC platform and then completed questions in the clinic or at home about completion status of a healthcare directive and durable power of attorney (DPOA) for healthcare, comfort in discussing ACP with their care team and loved ones, and goals of care at end of life. A summary of these responses with a provider prompt script was securely sent to the oncologist prior to each appointment and used to discuss ACP over the three-month study period. Descriptive statistics, t-tests, McNemar-Bowker and McNemar’s tests were conducted to examine changes in rates of ACP document completion, patient reported levels of comfort in discussing ACP, and quality of life preferences. Results: The study included a diverse sample of female MBC patients including 79% White, 19% Black/African American, 2% Mixed Race; 6% less than a high school degree, 17% high school or GED, 19% some college, and 58% associate’s degree or above. Results showed a significant increase in completion of a healthcare directive (Time 1 = 10.4%, Time 2 = 37.5%, p &lt; .01) and DPOA (Time 1 = 31.5%, Time 2 = 56.3%, p &lt; .01) and improved comfort discussing ACP with their care team (p &lt; .01) and loved ones (p &lt; .01) from baseline to follow-up. Significantly more patients reported that they would not want CPR (p &lt; .05) at follow-up and all of these patients had reported that they were unsure at baseline. On average, ACP conversations during medical appointment took 5 minutes to discuss. Conclusions: Results show that the ACAC is an inclusive solution which provides equitable access to patients. This tool facilitates enhanced patient provider communication and assists patients with MBC in finalizing decisions regarding their goals of care, leading to increased completion and proper submission of ACP documentation. Future research should examine how the ACAC can decrease financial toxicity, utilize internal resources, and address social determinants of health.
Defining germline genetics of germ cell tumor: Implications for genetic testing and clinical management.
Authors: Hong Truong, Vignesh Ravichandran, Yelena Kemel, Andrea Knezevic, Jack Patrick Gleeson, Nicole Benfante, Maria Bromberg, Mary Bolos, Gabriella Joseph, Richard Matulewicz, Joel Sheinfeld, Samuel Aaron Funt, Deaglan Joseph McHugh, Dean F. Bajorin, Mark Donoghue, Zsofia Kinga Stadler, Darren R. Feldman
Journal: Journal of Clinical Oncology (2022)

5007 Background: Epidemiologic studies on germ cell tumors (GCT) in men have shown GCT has a high heritability. Yet, the genetic mechanisms underlying development of GCT in men remain unknown. We sought to determine the prevalence of pathogenic or likely pathogenic (P/LP) germline variants in cancer predisposition genes in men with GCT and identify clinical and pathologic factors associated with the presence of P/LP variants. Methods: We retrospectively identified men with testicular (T) or mediastinal (M) GCT who underwent matched tumor--germline sequencing of ≥ 310 genes as part of an institutional genomic profiling initiative from 04/2015 to 12/2020. Presence of germline variants in clinically actionable genes associated with hereditary cancer syndromes were analyzed. Clinicopathologic characteristics, including primary site, histology and family history were assessed by the presence of P/LP variants and compared using Fisher’s exact test. Results: The study included 480 men, 70 (15%) with M-GCT and 410 (85%) with T-GCT. The median age of diagnosis was 30 years (interquartile range 24 – 39). A total of 81% had non-seminoma; 5% had localized disease; 46%, 14%, and 34% had good, intermediate, and poor risk advanced disease, respectively; 6% had family history of GCT. Among men with T-GCT, 4% had bilateral T-GCT. P/LP variants in clinically actionable genes were identified in 58 (12%) men in the entire cohort. Men with M-GCT had higher frequency of P/LP variants compared to those with T-GCT (15/70 [21%] vs 43/410 [10%], p = 0.02). A total of 7 (10%) men with M-GCT and 20 (5%) with T-GCT had P/LP variants in moderate or high penetrance cancer predisposition genes (p = 0.09). Most P/LP variants in both M-GCT (11/15, 73%) and T-GCT (33/43, 77%) were in genes involved in DNA damage repair pathways. The spectrum of moderate or high penetrance DNA damage repair genes identified is shown in the Table 1. Family history and histology (seminoma vs. non-seminoma) were not associated with the presence of a P/LP variants in the overall cohort (p = 0.8 and 0.7, respectively). Bilateral disease was not associated with the presence of P/LP variants in men with T-GCT (p = 0.4). Conclusions: Approximately 1 in 5 men with M-GCT carried a P/LP variant in a clinically actionable cancer susceptibility gene and 10% had a P/LP variant in a high-risk gene such as TP53 and PMS2. As men with GCT tend to develop disease in early adulthood, identification of germline P/LP variant has significant implications for enhanced cancer screening and surveillance, cascade testing for at-risk family members, and potential preconception genetic counseling. [Table: see text]
Outcomes in pleomorphic liposarcoma of the extremity and trunk: Is multimodality therapy indicated?
Authors: William W. Tseng, Francesco Barretta, Stefano Radaelli, Chiara Colombo, Dario Callegaro, Marta Barisella, Carlo Morosi, Roberta Sanfilippo, Chiara Fabbroni, Silvia Stacchiotti, Marco Fiore, Alessandro Gronchi
Journal: Journal of Clinical Oncology (2022)

e23545 Background: In comparison to the more common histologic subtypes of liposarcoma (e.g., well differentiated/dedifferentiated; myxoid round cell), pleomorphic liposarcoma (PLPS) is poorly understood but generally regarded as more aggressive, with a high risk of distant metastasis. In this study, we sought to 1) assess outcomes after surgery for primary, non-metastatic PLPS and 2) explore indications for multimodality therapy (e.g., perioperative chemotherapy, radiation therapy) in this ultra-rare malignancy. Methods: Clinicopathologic data were retrospectively collected for eligible adult patients treated from 2002-2019 at our sarcoma referral center. Descriptive data was summarized and Kaplan-Meier plots were constructed for overall survival (OS) and crude cumulative incidences (CCI) of disease-specific death (DSD), local recurrence (LR) and distant metastasis (DM). Univariable models were performed to assess the association of specific variables of interest (e.g., tumor size) on outcome. Results: In total, 51 PLPS patients were included in this study. Mean tumor size was 9.7 cm. Tumors originated mostly in the extremity (67%), were deep in location (73%), and high grade (FNCLCC 3/3, 78%). All patients underwent complete (R0/R1) resection. Chemotherapy was given in 33% of patients and radiation therapy in 69%. With a median follow-up of 62 months, OS was 76% at 5 years. CCI of DSD, LR and DM at 5 years was 16%, 2% and 26%. Greater tumor size was observed to be strongly associated with worse OS (p = 0.002) and DSD (p = 0.006). Survival did not seem to be affected by pre-referral inadequate excision once patients (n = 18) underwent re-excision at our center. A separate subgroup of patients (n = 14) was identified with smaller (mean: 5.4 cm), superficial, lower grade tumors who underwent surgery alone without any DSD. Conclusions: In primary, non-metastatic PLPS, adequate surgery combined with perioperative chemotherapy and radiation therapy, when appropriate, is associated with favorable outcomes. Subgroups with potentially better clinical outcomes likely exist suggesting heterogeneity within PLPS. Multidisciplinary collaborative efforts across sarcoma centers are needed to better characterize these subgroups and determine the optimal strategies for management.
Evaluation of tumor gene expression profile (GEP) in minority patients with stage IV non-small cell lung cancer (NSCLC).
Authors: Matthew Villanueva, Carlos Carracedo Uribe, Kayla Brice, Katerine Dumais, Olger Nano, Mitchelle Rodriguez, Elizabeth Osmon, Luis E. Raez
Journal: Journal of Clinical Oncology (2022)

e21043 Background: Differences in tumor gene expression profile (GEP) may contribute to disparities in lung cancer incidence and survival between racial and ethnic groups. For patients with stage IV NSCLC, tumor biomarker analysis is important for identification of potentially effective targeted therapies. However, despite advancements in biomarker testing and targeted therapy, minority patient enrollment in clinical trials remains low and it has been shown that minority patients are less likely to undergo next-generation sequencing (NGS) compared to Non-Hispanic Whites (NHW). As such, frequencies of tumor biomarkers in minority populations in the United States are not well-defined. This study aimed to determine the extent of tumor GEP diversity in minority patients vs NHW. Methods: This retrospective study included 196 adult patients with stage IV NSCLC that had a baseline NGS of tumor tissue or blood (liquid biopsy) performed between July 1, 2015 and June 30, 2021. Minority populations included Hispanic, African American, and Asian patients. Data collected utilizing the electronic medical record included patient demographics, detection of tumor biomarkers and treatment initiated. Descriptive statistics were calculated for all demographic and clinical variables. Comparisons of actionable epidermal growth factor receptor (EGFR) mutation frequency between NHW and minority patients were done using Chi-squared and Fisher’s exact tests. Results: Of the 196 patients evaluated, baseline characteristics included 46% male, 67% former smokers, 54% NHW, 31% Hispanic, 9% African American, 5% Asian, and 1% other. The median age at diagnosis was 66 ± 12 years. Actionable mutations (EGFR, KRAS, BRAF, ROS-1, ALK, MET, NTRK 1-3) were found in 50% of patients (see Table). The frequency of actionable EGFR mutations was higher in minority patients overall compared to NHW (39.3% vs 21.5%; p &lt; 0.01). The frequency of actionable EGFR mutations was similar between NHW and Hispanic patients (21.5% vs 27.9%; p = 0.35), however differences were observed comparing NHW to African American (21.5% vs 50%; p = 0.02) and Asian (21.5% vs 90%; p &lt; 0.01) patients, respectively. Conclusions: Among patients with stage IV NSCLC, the GEP of minority patients varied from that of NHW. Asian patients had the highest frequency of EGFR mutations, followed by African American and Hispanic patients, respectively. Larger studies are needed to validate these findings.[Table: see text]
Updated survival follow-up for phase I study of abexinostat with pazopanib in patients with solid tumor malignancies.
Authors: Erica S Tsang, Rahul Raj Aggarwal, Scott Thomas, Mallika Sachdev Dhawan, Nela Pawlowska, Imke Heleen Bartelink, Jennifer A. Grabowsky, Thierry Marie Jahan, Thach-Giao Truong, Charles J. Ryan, Pamela N. Munster
Journal: Journal of Clinical Oncology (2022)

3150 Background: Histone deacetylase (HDAC) inhibition downregulates HIF-1a, which may be effective in overcoming resistance to VEGF-targeting tyrosine kinase inhibitors. We report the updated survival follow-up for patients treated with abexinostat and pazopanib in a phase Ib trial. Methods: Patients with solid tumor malignancies were enrolled in this phase Ib, open-label trial (NCT01543763) of abexinostat in combination with pazopanib (3+3 design), with a dose expansion restricted to renal cell carcinoma (RCC). Patients received a 1-week run-in period with abexinostat alone, and then combination abexinostat with pazopanib during a 28-day treatment cycle until disease progression, unacceptable toxicity or study withdrawal. Plasma samples from 29 patients were sent for metabolomics analysis. Results: 51 patients were enrolled: N = 36 patients in dose escalation, N = 15 in dose expansion. At the time of last report in 2017, 5 patients remained on study treatment: N = 4 with RCC, and N = 1 with thymic neuroendocrine carcinoma. 4 of these patients have now had disease progression. Median duration of therapy measured 44.9 months (range 39.8-102.2). One patient with metastatic RCC (patient 1) remains on study treatment, after progression on 5 prior lines of systemic therapy. With updated survival follow-up, median OS measured 12.4 months in the dose escalation arm and 27.65 months in the RCC dose expansion cohort. Overall median duration of therapy in all 51 patients measured 5.6 months (range 1-103 months). Progression-free survival among patients with high PBMC HDAC2 expression (&gt; 0.4) remains longer compared to those with low expression (median 6.3 vs. 3.7 months, p = 0.0041). Metabolomics analysis demonstrated a negative correlation between HDAC2 and N6-acetyllysine, suggesting that baseline HDAC2 may impact efficacy of HDAC inhibition. Conclusions: The combination of abexinostat with pazopanib appears promising, with the potential for long-term responses particularly in patients with metastatic RCC. This has led to an ongoing phase III trial examining this combination in RCC. Clinical trial information: NCT01543763. [Table: see text]
Analysis of the likelihood of depression versus distress screening to identify need for intervention.
Authors: Valerie Pracilio Csik, Emma Hannan, Lauren Waldman, Greg D. Garber, Brooke Worster
Journal: Journal of Clinical Oncology (2022)

1544 Background: Psychosocial assessments are increasingly used to evaluate a patient-centered approach to quality cancer care delivery. Value-based oncology programs endorse screening metrics at every encounter. To comply with expectations of these programs, our cancer center utilizes two standardized tools: Patient Health Questionnaire (PHQ) to screen for depression at every encounter; National Comprehensive Cancer Network Distress Thermometer (NCCNDT) to screen for acute distress at clinically meaningful intervals. In 2021, oncology patients completed, on average, 5 annual appointments at Sidney Kimmel Cancer Center (SKCC), with a median appointment frequency of once every 19 days. Given the high encounter-per-patient ratio, we aimed to assess utility of frequent screening leading to supportive intervention. Methods: A retrospective analysis was conducted of medical oncology patients seeking care at SKCC with a completed depression and/or distress screening, as recorded in the patient’s electronic health record, between 1/1/2021 and 12/31/2021. This analysis intended to evaluate the percentage of patients whose scores indicate need for intervention. Patients who received more than one screening were attributed the highest score recorded during the measurement period. Results: A total 13,342 patients were screened at least once for either depression (n = 7,433), distress (n = 1,325), or both (n = 4,584). 3% of all patients screened ever met the intervention threshold (IT) for depression; 33% met the IT for distress. Of the patients who received both types of screenings, 31% met the IT for distress without meeting the threshold for depression. Those 1,418 patients would not have been referred for intervention through depression screening alone. Conclusions: This analysis highlights routine depression screening among a cancer population with a high encounter-per-patient ratio may not be sensitive in identifying need for supportive intervention. It also suggests that distress screening is more likely to lead to a supportive intervention than depression screening alone. This analysis combined with the anecdotal assessment by social workers supports the value of distress at clinically meaningful intervals over depression screening at each encounter. [Table: see text]
Risk of intracranial hemorrhage with direct oral anticoagulants versus low molecular weight heparin in glioblastoma: A retrospective cohort study.
Authors: Lauren Reed-Guy, Arati Suvas Desai, Richard Edmund Phillips, Desiree Croteau, Meghan O'Neill, Karen Albright, Steven Brem, Donald M. O'Rourke, Nduka Amankulor, Stephen Joseph Bagley
Journal: Journal of Clinical Oncology (2022)

2015 Background: Glioblastoma (GBM) is associated with a high rate of venous thromboembolism (VTE), but there is little data to guide anticoagulation in GBM patients, in whom the risks of VTE must be balanced against the risk of intracranial hemorrhage (ICH). Methods: We performed a single-institution retrospective cohort study of patients with GBM diagnosed with VTE from 2014-2021 who were treated with low molecular weight heparin (LMWH) or a direct oral anticoagulant (DOAC). The cumulative incidence of ICH was compared between the LMWH and DOAC groups. The primary outcome was clinically relevant ICH within the first 30 days of anticoagulation, defined as any ICH that was fatal, symptomatic, required surgical intervention, and/or led to cessation of anticoagulation. Key secondary outcomes included clinically relevant ICH within 6 months, fatal ICH within 30 days and 6 months, any bleeding within 30 days and 6 months, and recurrent VTE within 6 months. Fisher’s exact test was used for comparison of primary and secondary endpoints between the two groups. Cumulative incidence curves were generated using the Kaplan-Meier method, and the cumulative incidence of clinically relevant ICH at both the 30-day timepoint and 6-month timepoint was compared between the DOAC and LMWH groups using the Gray test to account for death as a competing risk. Results: A total of 121 patients were identified in the primary cohort for 30-day outcome analyses (DOAC, n = 33; LMWH, n = 88). For 6-month outcome analyses, the cohort included only patients who were maintained on their initial anticoagulant (DOAC or LMWH) and did not switch anticoagulants during the 6 months following diagnosis of VTE (DOAC, n = 32; LMWH, n = 75). The cumulative incidence of clinically relevant ICH at 30 days was 0% (0/33) in the DOAC group and 9% (8/88) in the LMWH group (p = 0.11). The cumulative incidence of clinically relevant ICH at 6 months was 0% (0/32) in the DOAC group and 24% (18/75) in the LMWH group (p = 0.001), with 4 fatal ICHs in the LMWH group. Other outcomes are displayed in the Table. Conclusions: Our study suggests that DOACs are associated with a lower incidence of clinically relevant ICH in patients with GBM-associated VTE compared to LMWH. These data support the use of DOACs as a safe alternative to LMWH in patients with GBM.[Table: see text]